Fungi are increasingly important in the production of many commercially-useful products. For example, filamentous fungi currently produce a number of metabolites on the industrial scale including antibiotics such as penicillins and cephalosporins, and organic acids such as citric and fumaric acids. Filamentous fungi are also used for the industrial production of enzymes such as proteases and lipases.
Utilization of a filamentous fungus species for production of a desired compound often involves growing submerged cultures of the fungus. Filamentous fungi can exhibit numerous morphologies in submerged cultures, including pelleted and “filamented” morphologies. When fungi in culture exhibit a filamented morphology, the presence of the filaments can increase the viscosity of the culture medium. The increased viscosity can affect the mass transfer and aeration properties of the culture, cause mixing problems in a bioreactor, and result in decreased productivity.
Alternatively, filamentous fungi can exhibit a pelleted morphology. In contrast to cultures of fungi exhibiting a filamented morphology, fungi cultures exhibiting a pelleted morphology can have relatively low viscosities and require substantially less power for mixing and aeration of the culture. Productivity for many compounds, for example citric acid, itaconic acid, statins, penicillins, and various enzymes, can be enhanced by utilizing fungus exhibiting a pelleted morphology. However, in certain fungal species, production of chemicals, for example peptic enzymes or fumaric acid, can be enhanced by utilizing a fungus exhibiting a filamented morphology. Typical practices in fungus-assisted chemical/protein production do not deliberately control the morphology of the fungus.
During fungal-morphology formation, a series of genes are up regulated or down regulated. To achieve optimal production of chemicals and/or proteins of interest, one can utilize the promoters and transcription terminators that exhibit strong constitutive expression of those genes. Concurrently, one can utilize induced gene expression at specific culture conditions and key stages in the cell's development to maximize gene expression and minimize adverse effects on fungal growth that may be associated with the enhanced production of certain chemicals and/or proteins. Thus a need exists for isolated fungal promoters and transcription terminators for regulation of gene expression in a fungus as well as methods for promoting enhanced production of desired chemicals and proteins.